Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University, And University of Fukui, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan; Department of Pharmacology, Graduate School of Dentistry, Osaka University, Osaka, 565-0871, Japan.
Biochem Biophys Res Commun. 2022 Nov 26;631:146-151. doi: 10.1016/j.bbrc.2022.09.079. Epub 2022 Sep 26.
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved pleiotropic neuropeptide, implicated in emotional stress responses and anxiety-related disorders. Here, we examined whether our recently developed small-molecule non-peptide PACAP receptor antagonists could ameliorate anxiety-like behaviors induced by acute restraint stress in mice. The antagonists PA-9 and its derivative PA-915 improved anxiety-like behaviors in mice subjected to restraint stress. An anxiolytic effect was observed with single acute dose, suggesting their fast-acting properties. PA-915 demonstrated a statistically significant anxiolytic effect whereas fluoxetine did not. These results indicate the potential of PAC1 antagonists as a novel treatment for anxiety.
垂体腺苷酸环化酶激活肽（PACAP）是一种高度保守的多功能神经肽，与情绪应激反应和焦虑相关障碍有关。在这里，我们研究了我们最近开发的小分子非肽类 PACAP 受体拮抗剂是否可以改善急性束缚应激诱导的小鼠焦虑样行为。拮抗剂 PA-9 和其衍生物 PA-915 改善了束缚应激小鼠的焦虑样行为。单次急性给药即可观察到抗焦虑作用，提示其具有快速作用的特性。PA-915 表现出统计学上显著的抗焦虑作用，而氟西汀则没有。这些结果表明 PAC1 拮抗剂作为一种新型焦虑治疗药物的潜力。
